Molecular design, synthesis and biological evaluation of BP-O-DAPY and O-DAPY derivatives as non-nucleoside HIV-1 reverse transcriptase inhibitors
| Autor: | Erik De Clercq, Christophe Pannecouque, Fen-Er Chen, Shi-Qiong Yang, Xiao-Dong Ma, Dirk Daelemans, Yang Liu |
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| Rok vydání: | 2012 |
| Předmět: |
Models
Molecular Efavirenz Nevirapine Stereochemistry Anti-HIV Agents Etravirine Microbial Sensitivity Tests chemistry.chemical_compound Zidovudine Benzophenones Structure-Activity Relationship Cell Line Tumor Drug Discovery medicine Delavirdine Humans Pharmacology Dose-Response Relationship Drug Molecular Structure Organic Chemistry virus diseases General Medicine Reverse transcriptase HIV Reverse Transcriptase Pyrimidines chemistry Rilpivirine Drug Design HIV-2 HIV-1 Reverse Transcriptase Inhibitors Nucleoside medicine.drug |
| Zdroj: | European journal of medicinal chemistry. 65 |
| ISSN: | 1768-3254 |
| Popis: | This paper reports the synthesis and antiviral evaluation of a series of non-nucleoside reverse transcriptase inhibitors (NNRTIs) that combine the peculiar structural features of diarylpyrimidine derivatives (DAPYs) and benzophenone derivatives (BPs). The DAPY derivatives bearing benzoyl or alkoxyl substitutes on the A-ring showed the inhibitory activity against wild-type HIV-1 at the cellular level within the range of EC50 values from micromolar to nanomolar. Among these compounds, 1u exhibited the most potent anti-HIV-1 activity (EC50 = 0.06 ± 0.01 μM, SI > 6260), which were about 1.8-fold more active than nevirapine (NVP) and delavirdine (DLV). In addition, the binding modes with HIV-1 RT and the preliminary SAR studies of these derivatives were also considered for further investigation. |
| Databáze: | OpenAIRE |
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